Heart regeneration has been a long-standing challenge due to the low proliferative ability of mammalian adult cardiomyocyte (CM) cells. CMs execute their final round of DNA synthesis and karyokinesis, become binucleated, and subsequently exit the cell cycle during the first week after birth. Although the remnants CMs possess certain degree of proliferation after a cardiac damage, the efficiency is low. Naqvi et al., Cell 157(4):795-807; 2014.
It was reported that somatic cells can be reprogrammed back to a pluripotent cell state similar to embryonic stem cells (ESCs) with high proliferative ability. Takahashi et al., Cell 126(4):663-676; 2006. Such reprogrammed cells are known as induced pluripotent stem cells (iPS cells or iPSCs). However, evidence in the art showed that CMs do have the potential to be reprogrammed. Xu et al., Cell Res. 22(1):142-154. Also, little was known regarding the detail mechanism or function at different time points for CMs to re-enter cell cycle.